CN114681654B

CN114681654B - Absorbable sponge dressing with wound repair function and preparation method thereof

Info

Publication number: CN114681654B
Application number: CN202011625073.1A
Authority: CN
Inventors: 张婧; 詹泽丰; 马骋; 邓坤学; 袁玉宇
Original assignee: Medprin Regenerative Medical Technologies Co Ltd
Current assignee: Medprin Regenerative Medical Technologies Co Ltd
Priority date: 2020-12-31
Filing date: 2020-12-31
Publication date: 2023-04-18
Anticipated expiration: 2040-12-31
Also published as: CN114681654A

Abstract

The invention provides an absorbable sponge dressing with a wound repairing function and a preparation method thereof. The sponge dressing comprises: a matrix comprising interwoven filaments; and a composite layer formed on at least one surface of the substrate, the composite layer being obtained by filling the substrate with a crosslinked degradable natural polymer material; and in the direction perpendicular to the sponge dressing, the maximum length of the composite layer is set to be H ₂ Assuming that the maximum length of the sponge dressing is H ₁ Then H is ₂ And H ₁ The ratio of (1). The sponge dressing provided by the invention has a certain function of absorbing seepage, and can simultaneously exert the function of promoting wound repair by a three-dimensional fiber structure. When in use, the matrix is attached to the wound surface, can effectively promote the creeping growth of cells of the wound surface, is beneficial to tissue repair and reduces the dressing change times.

Description

Absorbable sponge dressing with wound repair function and preparation method thereof

Technical Field

The invention relates to a sponge dressing and a preparation method thereof, in particular to an absorbable sponge dressing with a wound repairing function and a preparation method thereof, and belongs to the field of biomedical materials.

Background

The clinical common skin wound comprises acute wound and chronic wound. Wound healing is a complex process involving multiple cell types involved in the reconstruction of functional tissues. The normal wound healing is divided into four stages of hemostasis, inflammation, hyperplasia and remodeling. Acute wounds have a small wound area and can generally heal through a normal wound healing process. Severe acute wounds are also difficult to heal in a short period of time by the body's ability to heal. Chronic wounds (also called refractory wounds) resulting from persistent trauma, infection or potential conditions of ischemia, vascular disease, diabetes, etc., result in wounds that are difficult to heal due to a lack of effective inflammatory response involvement and a lack of available extracellular matrix.

With the intensive research on the pathophysiology of the wound healing process, people understand the wound healing process more and more deeply, thereby leading to the continuous improvement and development of wound dressings. Aiming at the field of wound care, a large number of dressing products are available in the market, the products have large dosage, low price and more types, and different types of dressings are used aiming at different stages of the wound.

Common dressings include hydrophilic dressings containing sodium carboxymethylcellulose hydrocolloid as a main component, absorbent dressings containing polymeric foam or alginate as a main component, dressings containing silver ions and having a bactericidal function, polymeric film dressings combining dressings and tapes, and acellular dermal matrix dressings capable of promoting wound repair. The hydrophilic and liquid-permeable absorbable dressing only has the functions of absorbing the liquid and maintaining the moist environment of the wound surface, does not have the function of promoting wound surface repair, is easy to adhere to the granulation tissue of the wound surface, and is easy to cause mechanical damage to the wound surface and increase pain of patients when changing the dressing. Acellular dermal matrix biological dressings have the effects of promoting cell crawling and providing an ECM (extracellular matrix) support for tissue growth, but have poor capability of absorbing seepage liquid and poor air permeability, and easily cause seepage liquid accumulation under the dressings on wound surfaces with more seepage liquid, so that the risk of infection is increased.

The selection of the dressing in clinic is beneficial to cell proliferation, differentiation and migration, maintains the moist environment of the wound surface, does not form dry scab, retains active substances in exudate and promotes the release of the active substances, has good air permeability, reduces the chance of infection, and does not cause mechanical damage to the wound surface when the dressing is replaced. The existing foam dressing for chronic wounds is usually applied to wounds with more seepage liquid, is used for absorbing the seepage liquid and maintaining the moist environment of the wounds, and the dressing does not have the function of promoting tissue repair. The existing film dressing (such as acellular dermal matrix dressing) has poor imbibition performance, and the absorption saturation is easy to cause the accumulation of the infiltration liquid under the membrane, possibly inducing or aggravating infection.

Therefore, the research on a sponge dressing with better seepage absorption capacity and tissue repair promoting function is a technical problem to be solved urgently.

Disclosure of Invention

Problems to be solved by the invention

In view of the technical problems in the prior art, the invention firstly provides the sponge dressing which has a double-layer structure, has better seepage absorption capacity and has the function of promoting tissue repair, can relieve the pain caused by dressing change, and can be gradually degraded along with the healing of a wound surface after being fused with a new tissue.

Furthermore, the invention also provides a preparation method of the sponge dressing, which is simple and feasible, has easily obtained raw materials and is suitable for mass production.

Means for solving the problems

The present invention provides a sponge dressing comprising:

a matrix comprising interwoven filaments; and

a composite layer formed on at least one surface of the substrate, the composite layer being obtained by filling the substrate with a cross-linked degradable natural polymer material; and is provided with

In the direction perpendicular to the sponge dressing, the maximum length of the composite layer is set to be H ₂ Assuming that the maximum length of the sponge dressing is H ₁ Then H is ₂ And H ₁ The ratio of (1) to (10).

Further, the sponge dressing has one or more of the following features:

the moisture absorption amount of the sponge dressing is 10-50 times of the self weight of the sponge dressing;

the porosity of the sponge dressing is 80-99%;

the bulk of the substrate is 300-3000 cm ³ /g。

Further, the fiber filaments are compounded by hydrophilic materials and hydrophobic materials; preferably, the mass ratio of the hydrophobic material to the hydrophilic material is 9.

Further, the hydrophilic material comprises one or the combination of more than two of polyvinyl alcohol, collagen, gelatin, chitosan, starch and agar; and/or

The hydrophobic material comprises one or the combination of more than two of polylactic acid, polyglycolide, polycaprolactone, polyvinyl alcohol, polyethylene terephthalate, polytetrafluoroethylene, polyvinylidene fluoride, polyurethane, polyesteramide, polymethyl methacrylate, polyhydroxybutyrate, polyethylene oxide, polyurethane and derivatives thereof and polycarbonate.

Further, the crosslinking is crosslinking in the presence of a crosslinking agent.

The invention also provides a preparation method of the sponge dressing, which comprises the step of forming a composite layer on at least one surface of the substrate.

Further, the preparation method comprises the following steps:

a step of obtaining a substrate;

dipping a part of the matrix in a solution containing a degradable natural polymer material in a direction perpendicular to the matrix to form a filling area, so that the filling area contains the degradable natural polymer material;

and freeze-drying the degradable natural polymer material in the filling area and then performing crosslinking treatment to form the composite layer.

Further, the matrix is prepared by the following preparation method:

obtaining a fiber material, wherein the fiber material comprises fiber filaments which are interwoven with each other;

alternately infiltrating the fiber material in a first solvent and a second solvent to swell the fiber filaments to obtain a swollen product, wherein the first solvent and the second solvent are different;

freezing the swollen product to obtain a frozen product;

and removing the first solvent and the second solvent in the frozen product to obtain the matrix.

Further, the preparation method comprises the following steps:

using a solution containing degradable natural polymer materials as a receiving device;

spinning the fiber raw material by using a spinning process, and forming a fiber material in the receiving device;

gelatinizing the solution containing the degradable natural polymer material, and then continuously spinning on the surface of the receiving device;

after spinning, carrying out freeze drying treatment, and carrying out crosslinking treatment on the degradable natural high polymer material to obtain a crosslinking treatment product;

alternately infiltrating the crosslinking treatment product in a first solvent and a second solvent to swell the fiber filaments to obtain a swollen product, wherein the first solvent and the second solvent are different;

freezing the swollen product to obtain a frozen product;

and removing the first solvent and the second solvent in the frozen product to obtain the sponge dressing.

Further, in the solution containing the degradable natural polymer material, the concentration of the degradable natural polymer material is 10-50wt%.

ADVANTAGEOUS EFFECTS OF INVENTION

The sponge dressing provided by the invention has a certain function of absorbing seepage, and can simultaneously exert the function of promoting wound repair by a three-dimensional fiber structure. When in use, the matrix is attached to the wound surface, can effectively promote the creeping growth of cells of the wound surface, is beneficial to tissue repair and reduces the dressing change times.

The preparation method of the sponge dressing is simple and feasible, the raw materials are easy to obtain, and the sponge dressing is suitable for mass production.

Drawings

FIG. 1 shows a schematic structural view of a sponge dressing of the present invention;

wherein, 1: a base; 2: and (3) compounding layers.

Figure 2 shows the application of the sponge dressing to the repair of scald defects in mouse skin, using HE sections (lower fold) at the wound site after 2 weeks, the filaments of the matrix promote the creeping growth of cells, wherein the dark colored portions are filaments that grow together with the tissue.

Fig. 3 shows that the sponge dressing is applied to repair the scald defect of the skin of the mouse, and the fusion condition of the cellosilk and the histiocyte can be obviously seen by using an HE section (with a higher multiple) at the position of the wound surface after 2 weeks.

Detailed Description

The present invention will be described in detail below. The technical features described below are explained based on typical embodiments and specific examples of the present invention, but the present invention is not limited to these embodiments and specific examples. It should be noted that:

in the present specification, the numerical range represented by "numerical value a to numerical value B" means a range including the end points of numerical values a and B.

In the present specification, "plural" in "plural", and the like means a numerical value of 2 or more unless otherwise specified.

In this specification, the terms "substantially", "substantially" or "substantially" mean an error of less than 5%, or less than 3% or less than 1% as compared to the relevant perfect or theoretical standard.

In the present specification, "%" represents mass% unless otherwise specified.

In the present specification, the meaning of "may" includes both the meaning of performing a certain process and the meaning of not performing a certain process.

In this specification, "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event occurs and instances where it does not.

In the present specification, reference to "some particular/preferred embodiments," "other particular/preferred embodiments," "embodiments," and the like, means that a particular element (e.g., feature, structure, property, and/or characteristic) described in connection with the embodiment is included in at least one embodiment described herein, and may or may not be present in other embodiments. In addition, it is to be understood that the described elements may be combined in any suitable manner in the various embodiments.

As shown in fig. 1, a first aspect of the present invention provides a sponge dressing comprising:

a substrate 1 comprising mutually interwoven filaments; and

a composite layer 2 formed on at least one surface of the substrate 1, the composite layer 2 being obtained by filling the substrate 1 with a cross-linked degradable natural polymer material; and is

In the direction perpendicular to the sponge dressing, the maximum length of the composite layer 2 is set as H ₂ Assuming that the maximum length of the sponge dressing is H ₁ Then H is ₂ And H ₁ The ratio of (1).

The sponge dressing has a certain function of absorbing seepage, and can play a role of promoting wound repair by a three-dimensional fiber structure.

Further, in the sponge dressing, the composite layer 2 can be directly formed in the substrate 1 to obtain the sponge dressing, or one substrate 1 can be used to form the composite layer 2, and then the composite layer 2 and the other substrate 1 are compounded and molded to obtain the sponge dressing; preferably, the composite layer 2 is formed directly in the substrate 1, so that a sponge dressing is obtained.

In some specific embodiments, the sponge dressing absorbs moisture in an amount of 10 to 50 times its own weight, for example: 15 times, 20 times, 23 times, 25 times, 28 times, 30 times, 35 times, 40 times, 45 times, etc. In particular, the moisture absorption amount of the present invention may be an amount of the sponge dressing capable of absorbing water or wound exudate. And the volume of the matrix 1 is reduced or unchanged during the process of adsorbing water. The sponge dressing has strong hygroscopicity, so that the sponge dressing can absorb wound exudate and reduce inflammatory reaction.

In the present invention, the method for measuring the moisture absorption amount is:

weighing a certain amount of sample (W) ₀ ) Adding distilled water (W) ₁ ) Wherein the mass ratio of the sample to the distilled water is 1. After swelling the sample for 5min until the sample is saturated with water, the remaining water is collected and filtered through a 30 μm sieve, denoted as W ₂ 。

Moisture absorption amount (times) = (W) ₁ -W ₂ )/W ₀ 。

In the present invention, the sponge dressing has a porosity of 80 to 99%, for example: 82%, 84%, 86%, 88%, 90%, 92%, 94%, 96%, 98%, etc. The matrix 1 of the invention can be directly contacted with the wound surface, and the porosity of the sponge dressing is high, so that the fiber of the extracellular matrix in the matrix 1 can promote the creeping growth of cells.

Specifically, the porosity of the sponge dressing was measured as follows:

first, the desired dry weight of the sample is weighed as M ₀ The weighed sample is placed into a clean beaker, and ethanol is injected into the beaker until the sample is submerged. After the sample is completely soaked, quickly taking out the sample, putting the sample into a small basket prepared for weighing, hanging the basket on a lifting hook of a balance to enable the sample to be continuously immersed into ethanol, weighing the suspended weight of the saturated sample in the ethanol, and recording the suspended weight as M ₁ The saturated sample was taken out, ethanol on the surface of the saturated sample was carefully wiped off with a wet rag, and the mass of the saturated sample was quickly weighed and recorded as M ₂ . The porosity was calculated by the following formula:

P＝(M ₂ -M ₀ )/(M ₂ -M ₁ )。

substrate

The matrix 1 of the present invention is a nanofiber sponge. In the present invention, the matrix 1 comprises interwoven filaments.

In some specific embodiments, the bulk of the substrate 1 is 300 to 3000cm ³ G, for example: 500cm ³ /g、800cm ³ /g、1000cm ³ /g、1200cm ³ /g、1500cm ³ /g、1800cm ³ /g、2000cm ³ /g、2200cm ³ /g、2500cm ³ /g、2800cm ³ And/g, etc. The base 1 of the present invention has high bulk and high moisture absorption.

The bulk degree of the invention is 1000 times of the ratio of the apparent thickness to the surface density of the substrate 1, namely:

bulk B = apparent thickness T ₀ Areal density ω x 10 ³

Bulk in cm ³ Expressed in terms of/g, the apparent thickness in mm and the areal density in g/m ² And (4) showing. Apparent thickness T ₀ The test method is to use FAST-1 compressive fabric style instrument to test according to GB/T7689.1-2001 method, and the expression is that the matrix 1 is at 2cN/cm ² Thickness (mm) under pressure of 100cN/cm of substrate 1 ² Difference in thickness (mm) under pressure. The surface density ω was measured by measuring the weight per unit area of the single surface regardless of the thickness of the substrate 1.

Further, the source of the fiber yarn of the present invention is not particularly limited, and it may be spun by a spinning process commonly used in the art. In particular, the matrix 1 of the invention is derived from a fibrous material comprising interwoven fibre filaments. The fiber material of the present invention can be produced by electrospinning, melt spinning, centrifugal force spinning, or the like, and is preferably produced by electrospinning. The fibrous material may be a mass of fibers, a bundle of fibers or a film of fibers, preferably a film of fibers. In the present invention, the diameter of the filament may be 1nm to 100. Mu.m, preferably 100nm to 5 μm.

The principle of electrospinning is that a high voltage is applied to a polymer liquid during electrospinning to introduce electrical charges into the liquid. When charges in the liquid are accumulated to a certain amount, the liquid can form a Taylor cone at the spray head, liquid jet flow is formed by overcoming surface tension under the action of an external electric field force, and then polymer jet flow moves along an irregular spiral track under the combined action of electrostatic repulsion, coulomb force (Coulomb) and surface tension. The jet is drawn and stretched in a very short time, and as the solvent evaporates or heat is dissipated, the polymer jet solidifies to form the micro/nano fibers. In the electrostatic spinning process, a plurality of parameters can influence the final electrostatic spinning fiber, and the micron/nanometer fibers with different sizes, shapes and structures can be prepared and obtained by controlling the process parameters.

In the electrostatic spinning process, the technological parameters can influence the fiber materials obtained by electrostatic spinning, and the fiber materials with different sizes, forms and structures can be prepared and obtained by controlling the technological parameters. The present invention is not particularly limited to the electrospinning method, and may be any electrospinning method commonly used in the art. Specifically, the raw materials for forming the fiber material are dissolved in a proper solvent to prepare a spinning solution; and then spinning the spinning solution into a fiber material formed by interweaving fiber yarns by adopting electrostatic spinning.

Further, the fiber yarn of the present invention comprises a hydrophilic material and a hydrophobic material, and preferably, the fiber yarn of the present invention is formed by compounding the hydrophilic material and the hydrophobic material. Because the hydrophilic material and the hydrophobic material have different infiltration effects in different solvents, after treatment, the fiber material can expand, so that a swelling effect is formed, and the matrix 1 of the application is further obtained.

Preferably, from the production point of view, the mass ratio of the hydrophobic material to the hydrophilic material is 9:1, 8, 7. When the mass ratio of the hydrophobic material to the hydrophilic material is 9 to 1.

In some specific embodiments, the hydrophilic material comprises one or a combination of two or more of polyvinyl alcohol, collagen, gelatin, chitosan, starch, agar, and the like. The hydrophobic material comprises one or the combination of more than two of polylactic acid, polyglycolide, polycaprolactone, polyvinyl alcohol, polyethylene terephthalate, polytetrafluoroethylene, polyvinylidene fluoride, polyurethane, polyesteramide, polymethyl methacrylate, polyhydroxybutyrate, polyethylene oxide, polyurethane and derivatives thereof, polycarbonate and the like.

Composite layer

The composite layer 2 of the present invention is formed on at least one surface of the substrate 1, and the composite layer 2 is obtained by filling the substrate 1 with a cross-linked degradable natural polymer material; and is provided with

In the direction perpendicular to the sponge dressing, the maximum length of the composite layer 2 is set as H ₂ Assuming that the maximum length of the sponge dressing is H ₁ ，H ₂ And H ₁ The ratio of (1): 1.

In the present invention, the degradable natural polymer material may be, for example, gelatin and/or collagen. The use of gelatin and/or collagen enables the most effective performance of the sponge dressing.

The crosslinking of the invention can be obtained by crosslinking modification treatment of degradable natural polymer materials. Specifically, the crosslinking modification is a crosslinking modification in the presence of a crosslinking agent, thereby obtaining a crosslinked product which is suitable in the degree of crosslinking and uniform.

In the present invention, the purpose of the crosslinking modification is to make the degradable natural polymer material absorb a large amount of liquid and maintain the shape well, so that the degradable natural polymer material is not dissolved by absorbed body fluid quickly. Specifically, the cross-linking agent comprises one or the combination of more than two of carbodiimide/N-hydroxysuccinimide, genipin and aldehyde compounds; specifically, the aldehyde compound comprises one or more of formaldehyde, acetaldehyde and glutaraldehyde, and more preferably comprises glutaraldehyde.

Further, in some specific embodiments, the thickness of the substrate 1 is the thickness of the sponge dressing, and the composite layer 2 is formed by filling a part of the substrate 1 with a cross-linked degradable natural polymer material. Preferably, the difference between the thickness of the sponge dressing and the thickness of the composite layer 2 is 1-20mm, for example: 2mm, 4mm, 6mm, 8mm, 10mm, 12mm, 14mm, 16mm, 18mm, and the like.

A second aspect of the present invention provides a method of manufacturing a sponge dressing according to the first aspect of the present invention, comprising the step of forming a composite layer 2 on at least one surface of the substrate 1. The preparation method is simple and feasible, the raw materials are easy to obtain, and the preparation method is suitable for mass production.

The matrix 1 of the invention can exist in the microscopic shape of the nano-fiber, and the combination of more nano-fibers presents the shape of a sponge. In addition, the nanofiber can simulate the natural extracellular matrix (ECM) of a human body on the form and structure, so that the adhesion and proliferation of cells are facilitated, and the sponge has ultrahigh porosity and specific surface area, so that the sponge dressing is very soft and has strong adsorption performance.

< first preparation method >

In some specific embodiments, the method of preparation may comprise the steps of:

a step of obtaining a substrate 1;

immersing a portion of the substrate 1 in a solution containing a degradable natural polymer material in a direction perpendicular to the substrate 1 (Z direction in fig. 1) to form a filled region containing the degradable natural polymer material;

the degradable natural polymer material in the filling area is subjected to freeze drying and then cross-linking treatment to form the composite layer 2.

Step of obtaining the substrate

In the invention, the matrix 1 is prepared by the following preparation method:

freezing the swollen product to obtain a frozen product;

and removing the first solvent and the second solvent in the frozen product to obtain the matrix 1.

Specifically, the fiber filaments are compounded by hydrophilic materials and hydrophobic materials; the fiber material can be prepared by electrostatic spinning, melt spinning, centrifugal force spinning and other modes. In general, the thickness of the fibrous material may be 100-500 microns.

In some specific embodiments, the present invention uses an electrospinning process to produce the resulting fibrous material. Specifically, in the electrospinning step, a fiber raw material is prepared in advance, and the fiber raw material is dissolved in a suitable solvent to prepare a spinning dope of the fiber raw material at a certain concentration, preferably, the concentration of the spinning dope is 3 to 25% (mass/volume ratio). Wherein the fiber raw material may be the hydrophilic material and the hydrophobic material in the first embodiment. The specific concentration of the solvent species forming the solution is not particularly limited as long as the requirements of the subsequent electrospinning process can be met. For example, suitable solvents may be one or a combination of two or more of formic acid, acetic acid, acetone, dimethylformamide, dimethylacetamide, tetrahydrofuran, dimethylsulfoxide, hexafluoroisopropanol, trifluoroethanol, dichloromethane, chloroform, and trifluoroacetic acid.

The required fiber material can be prepared by adjusting spinning parameters in the electrostatic spinning process. Such as voltage, extrusion flow and electric field acceptance distance, spinning environment, etc. Preferably, the electrostatic spinning process parameters in the present invention may be: the pressure is 10-40 kV, the solution propelling speed is 2.5 mL/h-10 mL/h; the receiving distance can be 10 cm-50 cm, the environment temperature is controlled to be 18-30 ℃, and the relative humidity of the spinning environment is 40-80%.

Further, the fiber material is alternately soaked in a first solvent and a second solvent to swell the fiber filaments to obtain a swollen product, wherein the first solvent and the second solvent are different. Because the two raw materials of the fiber material have different soaking effects in different solvents, the fiber yarn can be expanded to form a swelling effect. In the present invention, the first solvent and the second solvent are not particularly limited and may be determined according to the fiber raw material.

In some specific embodiments, the first solvent is water, and the second solvent is not particularly limited and may be selected according to the characteristics of the hydrophobic material. Specifically, the second solvent is one or a combination of two or more of methanol, ethanol, propanol, propylene glycol, acetone, tetrahydrofuran, and the like. The fiber material is soaked in the first solvent for a certain time and then is soaked in the second solvent, and because the hydrophilic material and the hydrophobic material are contained in the fiber material, the hydrophilic material is completely soaked in the aqueous solution, but the hydrophobic material cannot be soaked, the hydrophobic material can be well soaked in the second solvent, so that the fiber material can be swelled to a certain thickness after being soaked alternately for multiple times.

By "alternating immersion" is meant in the present invention immersion in a first solvent for a period of time, followed by immersion in a second solvent for a period of time after removal. The number of times of alternation is not particularly limited, and may be arbitrarily set as required. For example, the amount of the solvent, the soaking time and the number of times required are determined according to the condition of the residual solvent. Specifically, the first solvent may be soaked 1 to 10 times, and the second solvent may be soaked 1 to 10 times.

In some specific embodiments, the total time of immersion in the first solvent is 15 to 120min, for example: 30min, 45min, 60min, 75min, 90min, 105min and the like; and/or the total time of immersion in the second solvent is 15 to 120min, for example: 30min, 45min, 60min, 75min, 90min, 105min and the like. After infiltration, a bulk material (i.e., a swelling product) can be obtained which swells the fiber material by 25 to 100 times.

The invention obtains a frozen product by freezing the swelling product. The swollen product can be kept in its structural form by the step of freezing. In some specific embodiments, the freezing temperature is from-20 ℃ to-85 ℃, for example: -25 ℃, -30 ℃, -35 ℃, -40 ℃, -45 ℃, -50 ℃, -55 ℃, -65 ℃, -70 ℃, -75 ℃, -80 ℃ and the like; the freezing time is 24 hours or more, for example: 28 hours, 32 hours, 36 hours, 40 hours, 44 hours, 48 hours, 52 hours, 56 hours, 60 hours, etc.

Further, in some embodiments, during freezing, after the swelling product has finished freezing to a fixed shape, it can be removed and cut to a desired size. In addition, the temperature during the cutting process is not too low, and may be generally from-10 ℃ to-20 ℃, for example, from-11 ℃, to-12 ℃, to-13 ℃, to-14 ℃, to-15 ℃, to-16 ℃, to-17 ℃, to-18 ℃, to-19 ℃. Then, the freezing is continued for not less than 8 hours, for example: 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, 24 hours, 28 hours, 32 hours, 36 hours, etc.

The freezing apparatus of the present invention is not particularly limited, and may be a low-temperature refrigerator commonly used in the art.

The invention finally makes it possible to obtain the matrix 1 by removing the first solvent and the second solvent from the frozen product. It is still desirable to keep the structure of the frozen product from being damaged while removing the first and second solvents from the frozen product.

In some embodiments, the first solvent and the second solvent in the frozen product may be vaporized by freeze-drying to remove the first solvent and the second solvent. By removing the first solvent and the second solvent from the frozen product under vacuum by freeze-drying, the structure of the frozen product can be maintained, thereby forming the matrix 1.

In some specific embodiments, the temperature of the freeze-drying is from-40 ℃ to-80 ℃, for example: -45 ℃, -50 ℃, -55 ℃, -60 ℃, -65 ℃, -70 ℃, -75 ℃ and the like; the freeze-drying time is 1 to 3 days, for example, 1.2 days, 1.5 days, 1.8 days, 2 days, 2.2 days, 2.5 days, 2.8 days, etc.

Specifically, the fiber material with the structure completely frozen and fixed is placed into a freeze dryer, the temperature of a cold trap is set to be reduced to-40 ℃ to-80 ℃, after the temperature of the cold trap is reduced to the set temperature, a vacuum pump is started, and freeze drying is carried out, so that the matrix 1 is obtained.

Step of Forming composite layer

After obtaining the matrix 1, immersing a part of the matrix 1 in a solution containing a degradable natural polymer material in a direction perpendicular to the matrix 1 (Z direction in fig. 1) to form a filled region containing the degradable natural polymer material; the degradable natural polymer material in the filling area is subjected to freeze drying and then cross-linking treatment to form the composite layer 2.

In some specific embodiments, in order to allow the degradable natural polymer material to fill the filling region, the concentration of the degradable natural polymer material in the solution containing the degradable natural polymer material is 10 to 50wt%.

Further, as for the position and height of the filled region, it is general that the non-impregnated surface of the base 1 exceeds the surface of the solution containing the degradable natural polymer material by 1 to 20mm.

In some specific embodiments, the solution containing the degradable natural polymer material is freeze-dried after filling the filling area. The temperature of the freeze drying is-40 ℃ to-80 ℃, for example: minus 45 ℃, minus 50 ℃, minus 55 ℃, minus 60 ℃, minus 65 ℃, minus 70 ℃, minus 75 ℃ and the like; the freeze-drying time is 1 to 3 days, for example, 1.2 days, 1.5 days, 1.8 days, 2 days, 2.2 days, 2.5 days, 2.8 days, etc.

Specifically, freeze-drying is performed in a freeze-dryer. And (3) setting the temperature of the cold trap to be reduced to-40 to-80 ℃, starting a vacuum pump after the temperature of the cold trap is reduced to the set temperature, performing freeze drying, removing the solvent and obtaining a freeze-dried product.

Further, the degradable natural polymer material in the freeze-dried product is subjected to cross-linking treatment to form the composite layer 2. Specifically, the crosslinking is crosslinking in the presence of a crosslinking agent. Further, the temperature of the cross-linking treatment is 10-70 ℃, preferably 25-50 ℃; the time of the crosslinking treatment is 1 to 72 hours, preferably 12 to 72 hours.

In the crosslinking step, the selected crosslinking agent comprises one or the combination of more than two of carbodiimide/N-hydroxysuccinimide, genipin and aldehyde compounds. Specifically, the aldehyde compound comprises one or more of formaldehyde, acetaldehyde and glutaraldehyde, and more preferably comprises glutaraldehyde.

In some specific embodiments, the present invention further comprises a post-treatment step, wherein the cross-linked product obtained by the above cross-linking treatment is post-treated to obtain the final sponge dressing. The mode of the post-treatment is not particularly limited, and post-treatment methods generally used in the art, including washing, drying, classification, packaging, and the like, can be used.

The washing may be carried out using water and/or an organic solvent such as a low-boiling hydrocarbon, an alcohol, an ether, or a ketone, and is preferably carried out using water. The drying may be carried out under refrigerated conditions to obtain a dried product.

< preparation Process two >

In other specific embodiments, the method of making may comprise the steps of:

freezing the swollen product to obtain a frozen product;

Specifically, in the solution containing the degradable natural polymer material, the concentration of the degradable natural polymer material is 10-50wt%. The present invention uses the solution containing the degradable natural polymer material as a receiving device. Preferably, the depth of the receiving means is 1-10mm.

Further, the present invention utilizes a spinning process to spin the fiber feedstock and form the fiber material in the receiving device. The present invention is not particularly limited to the spinning process, and may be any spinning process in the art. Specifically, the fiber material can be prepared by electrostatic spinning, melt spinning, centrifugal spinning and other modes; the fiber material of the invention comprises fiber filaments which are interwoven with each other through a spinning process. Specifically, the fiber yarn is formed by compounding a hydrophilic material and a hydrophobic material.

In some specific embodiments, the present invention uses an electrospinning process to produce the resulting fibrous material. Specifically, in the electrospinning step, a fiber raw material is prepared in advance, and the fiber raw material is dissolved in a suitable solvent to prepare a spinning solution of the fiber raw material at a certain concentration, preferably, the concentration of the spinning solution is 3 to 25% (mass/volume ratio). Wherein the fiber raw material may be the hydrophilic material and the hydrophobic material in the first embodiment. The specific concentration of the solvent species forming the solution is not particularly limited as long as the requirements of the subsequent electrospinning process can be met. For example, suitable solvents may be one or a combination of two or more of formic acid, acetic acid, acetone, dimethylformamide, dimethylacetamide, tetrahydrofuran, dimethylsulfoxide, hexafluoroisopropanol, trifluoroethanol, dichloromethane, chloroform, and trifluoroacetic acid.

And (3) gelling the solution containing the degradable natural polymer material when the thickness of the spinning product is basically level with that of the receiving device, and then continuously spinning on the surface of the receiving device. The mode of gelation is not particularly limited in the present invention, and a solution containing a degradable natural polymer material may be gelled. Preferably, the solution containing the degradable natural polymer material can be gelled by cooling. Specifically, the temperature after temperature reduction may be 0 to 10 ℃, for example: 1 deg.C, 2 deg.C, 3 deg.C, 4 deg.C, 5 deg.C, 6 deg.C, 7 deg.C, 8 deg.C, 9 deg.C, etc.

And (4) after spinning is finished, carrying out freeze drying treatment. The temperature of the freeze drying is-40 ℃ to-80 ℃, for example: minus 45 ℃, minus 50 ℃, minus 55 ℃, minus 60 ℃, minus 65 ℃, minus 70 ℃, minus 75 ℃ and the like; the freeze-drying time is 1 to 3 days, for example, 1.2 days, 1.5 days, 1.8 days, 2 days, 2.2 days, 2.5 days, 2.8 days, etc.

And further, crosslinking the degradable natural high molecular material in the freeze-dried product to obtain a crosslinked product. Specifically, the crosslinking is crosslinking in the presence of a crosslinking agent.

Further, alternately infiltrating the crosslinking treatment product in a first solvent and a second solvent to swell the fiber filaments to obtain a swollen product, wherein the first solvent and the second solvent are different; because the two raw materials of the fiber material have different soaking effects in different solvents, the fiber yarn can be expanded to form a swelling effect. In the present invention, the first solvent and the second solvent are not particularly limited and may be determined according to the fiber raw material.

In some specific embodiments, the first solvent is water, and the second solvent is not particularly limited and may be selected according to the characteristics of the hydrophobic material. Specifically, the second solvent is one or a combination of two or more of methanol, ethanol, propanol, propylene glycol, acetone, tetrahydrofuran, and the like. The fiber material is soaked in the first solvent for a certain time and then is soaked in the second solvent, and the hydrophilic material and the hydrophobic material are completely soaked in the aqueous solution and cannot be soaked in the aqueous solution, so that the hydrophobic material can be well soaked in the second solvent, and the fiber material can be swelled to a certain thickness after being alternately soaked for multiple times.

By "alternating immersion" is meant in the present invention immersion in a first solvent for a period of time, followed by immersion in a second solvent for a period of time after removal. The number of times of alternation is not particularly limited, and may be arbitrarily set as required. For example, the amount of the solvent, the soaking time and the number of times are determined according to the condition of the residual solvent. In some specific embodiments, the total time of immersion in the first solvent is 15 to 120min, for example: 30min, 45min, 60min, 75min, 90min, 105min and the like; and/or the total time of immersion in the second solvent is 15 to 120min, for example: 30min, 45min, 60min, 75min, 90min, 105min and the like; and/or the alternate soaking times in the two solvents are 2 times, 3 times, 4 times, 6 times and the like. After infiltration, a bulk material (i.e., a swelling product) which swells the fiber material by 25 to 100 times can be obtained.

The invention obtains a frozen product by freezing the swelling product. The swollen product can be kept in its structural form by the step of freezing. In some specific embodiments, the freezing temperature is from-20 ℃ to-85 ℃, for example: 25 ℃ below zero, 30 ℃ below zero, 35 ℃ below zero, 40 ℃ below zero, 45 ℃ below zero, 50 ℃ below zero, 55 ℃ below zero, 65 ℃ below zero, 70 ℃ below zero, 75 ℃ below zero, 80 ℃ below zero, and the like; the freezing time is 24 hours or more, for example: 28 hours, 32 hours, 36 hours, 40 hours, 44 hours, 48 hours, 52 hours, 56 hours, 60 hours, etc.

Further, in some embodiments, during freezing, after the swelling product has finished freezing to a fixed shape, it can be removed and cut to a desired size. In addition, the temperature during the cutting process is not too low, and may be generally from-10 ℃ to-20 ℃, for example, from-11 ℃, to-12 ℃, to-13 ℃, to-14 ℃, to-15 ℃, to-16 ℃, to-17 ℃, to-18 ℃, to-19 ℃. Then, the freezing is continued for not less than 8 hours, for example: 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, 24 hours, 28 hours, 32 hours, 36 hours, etc. The freezing apparatus of the present invention is not particularly limited, and may be a low-temperature refrigerator commonly used in the art.

The present invention can obtain the matrix 1 by removing the first solvent and the second solvent from the frozen product. It is still desirable to keep the structure of the frozen product from being damaged while removing the first and second solvents from the frozen product.

In some embodiments, the first solvent and the second solvent in the frozen product may be vaporized by freeze-drying to remove the first solvent and the second solvent. The structure of the frozen product can be kept by adopting a freeze drying mode and removing the first solvent and the second solvent in the frozen product in a vacuum state, so that the sponge dressing is formed.

In some specific embodiments, the temperature of the freeze-drying is from-40 ℃ to-80 ℃, for example: minus 45 ℃, minus 50 ℃, minus 55 ℃, minus 60 ℃, minus 65 ℃, minus 70 ℃, minus 75 ℃ and the like; the freeze-drying time is 1 to 3 days, for example: 1.2 days, 1.5 days, 1.8 days, 2 days, 2.2 days, 2.5 days, 2.8 days, etc. Specifically, the product which is completely frozen and fixed by the structure is put into a freeze dryer, the temperature of a cold trap is set to be reduced to-40 ℃ to-80 ℃, and after the temperature of the cold trap is reduced to the set temperature, a vacuum pump is started for freeze drying.

Finally, the obtained sponge dressing can be cut, hermetically packaged and then sterilized by irradiation. For example: co-60 gamma ray irradiation can be adopted for sterilization treatment.

The third aspect of the invention provides the application of the sponge dressing of the first aspect and the sponge dressing prepared by the preparation method of the second aspect in preparing medical materials such as injury repair products, bone filling repair scaffolds, biological scaffolds and the like.

In particular, the sponge dressing can be used for hemostasis and repairing chronic wounds or injuries with more seepage. In addition, the sponge dressing can be compounded with a high-strength supporting layer, crosslinked and the like to enhance the mechanical property of the bracket, so that the softness of the whole bracket is obviously improved due to the super-soft property of the sponge dressing, and the sponge dressing can be used for repairing skin, soft tissue and other injuries. And hydroxyapatite and other materials can also be filled in the sponge dressing to obtain a good bone filling and repairing scaffold. The ultra-high porosity of the sponge dressing can adsorb growth factors, medicines and the like, and the biological scaffold containing the growth factors or the medicines is obtained. The sponge dressing has wide application prospect in medical fields such as bionics, tissue engineering and the like.

Examples

Embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.

Example 1

The preparation method comprises the following steps of selecting hydrophobic materials polyglycolide and hydrophilic materials gelatin, wherein the mass ratio of the polyglycolide to the gelatin is 9. The solution was filled into a syringe and mounted on a propeller pump associated with the electrospinning machine. The electrostatic spinning was carried out under the conditions of a voltage of 40kV, a forwarding speed of 8mL/h, a reception distance of 30cm, an ambient temperature of 25 ℃ and an ambient humidity of 50%. The final film thickness ranges from 180 to 230 microns and the fiber diameter ranges from 0.8 to 25 microns.

Soaking the fiber membrane in methanol for 30min, soaking the soaked fiber membrane in water for 30min, and alternately soaking until the fiber membrane swells to form a block material with the thickness increased by 30 times. Placing the swollen block material in a suitable tray, and freezing in a refrigerator at-40 deg.C for at least 24 hr. Freeze drying the frozen block material, removing the soaked solvent and retaining the swollen structure of the fiber membrane to form a fiber sponge, wherein the bulk density of the fiber sponge is 500cm ³ /g。

Preparing a 10wt.% gelatin solution, and soaking a part of the fiber sponge in the gelatin solution, wherein the surface of the fiber sponge exceeds the surface of the gelatin solution by 3mm. And (3) after the gelatin solution is filled in pores of the fiber membrane, carrying out freeze drying, setting the temperature of the cold trap to be reduced to-60 ℃, starting a vacuum pump after the temperature of the cold trap is reduced to the set temperature, carrying out freeze drying, removing the solvent and obtaining a freeze-dried product, wherein the freeze-drying time is 48h (2 days). And (3) carrying out crosslinking treatment on gelatin in the dried product by using glutaraldehyde, wherein the crosslinking condition is modification treatment for 48 hours at 20 ℃, washing with deionized water to remove the crosslinking agent, and then carrying out freeze drying again to finally obtain the absorbable sponge dressing with the double-layer structure. The porosity of the final sponge dressing was 90% and the moisture absorption was about 20 times the weight of the sponge dressing itself. Wherein, the thickness of sponge dressing is 5mm, and the thickness of composite bed 2 is 2mm.

The effect of the dressing is represented by adopting an animal experiment, the sponge is used for repairing the scald defect of the skin of the mouse, and the result shows that the sponge dressing can well promote tissue repair when fibers and tissues grow together, and particularly, the sponge dressing can be seen in fig. 2 and 3.

Example 2

A gelatin solution with a concentration of 20wt.% was prepared and placed in a temperature-controlled vessel, the temperature being maintained at 40 ℃.

The polylactic acid is selected as a hydrophobic material, the gelatin is selected as a hydrophilic material, and the mass ratio of the polylactic acid to the gelatin is 2. Chloroform was selected as the organic solvent to prepare a viscous solution with a final concentration of 10 wt.%. The solution was filled into a syringe and mounted on a propeller pump associated with the electrospinning machine. A gelatin solution with a temperature controlled at 40 ℃ is used as a receiving device, and the depth of the solution is 10mm. The electrostatic spinning was carried out under the conditions of a voltage of 30kV, a forwarding speed of 3mL/h, a reception distance of 20cm, an ambient temperature of 25 ℃ and an ambient humidity of 70%. After the 10mm depth solution was filled with the fiber filaments, the gelatin solution vessel temperature was adjusted to 5 ℃ to gel the gelatin. Spinning is continued, and the spun silk forms a membrane sheet on the surface of the gel, wherein the thickness of the membrane sheet ranges from 200 to 250 micrometers, and the diameter of the fiber ranges from 1 to 15 micrometers.

After spinning is finished, the gelatin-polylactic acid-gelatin compound is subjected to freeze drying, the temperature of a cold trap is set to be-50 ℃, after the temperature of the cold trap is reduced to the set temperature, a vacuum pump is started for freeze drying, a solvent is removed, and a freeze-dried product is obtained, wherein the freeze-drying time is 48h (2 days). And (3) crosslinking the gelatin in the dried product by using genipin, wherein the crosslinking condition is modification treatment for 72 hours at 30 ℃. And after crosslinking, soaking the crosslinked product in ethanol for 80min, then soaking the soaked crosslinked product in water for 80min, and alternately soaking until the whole compound swells to form a block material with the thickness increased by 80 times.

Placing the swelled block material in a suitable tray, and freezing in an ultra-low temperature refrigerator at-80 deg.C for at least 24 hr. And (3) freeze-drying the frozen massive material, removing the soaked solvent and reserving the structure of the fiber membrane after swelling, and finally obtaining the absorbable sponge dressing with the double-layer structure. The bulkiness of the fiber sponge is 2500cm ³ The porosity of the whole sponge dressing is 93 percent. Wherein, the thickness of the sponge dressing is 26mm, the thickness of the composite layer 2 is 10mm, and the moisture absorption capacity is about 35 times of the self weight of the sponge dressing.

The effect of the dressing is represented by adopting an animal experiment, the sponge is used for repairing the skin defect of the diabetic pig, and the result shows that the sponge dressing can well promote tissue repair when fibers and tissues grow together.

Example 3

The preparation method comprises the following steps of selecting a hydrophobic material polycaprolactone and a hydrophilic material polyvinyl alcohol, wherein the mass ratio of the polycaprolactone to the polyvinyl alcohol is 1. The solution was filled into a syringe and mounted on a propeller pump associated with the electrospinning machine. The electrostatic spinning was carried out under the conditions of a voltage of 36kV, a forwarding speed of 6mL/h, a receiving distance of 40cm, an ambient temperature of 25 ℃ and an ambient humidity of 70%. The final film thickness ranges from 250 to 310 microns and the fiber diameter ranges from 1.5 to 40 microns.

And soaking the fiber membrane in acetone for 50min, soaking the soaked fiber membrane in water for 50min, and alternately soaking until the fiber membrane swells to form a block material with the thickness increased by 90 times. The above swollen bulk material was placed in a suitable tray and then frozen in a freezer at-40 ℃ for 36h. And freeze-drying the frozen massive material, removing the soaked solvent and reserving the swollen structure of the fiber membrane to form the fiber sponge. The fiber sponge has a bulk of 2800cm ³ /g。

Preparing a gelatin solution with the concentration of 40wt.%, and soaking a part of the fiber sponge in the gelatin solution, wherein the surface of the fiber sponge exceeds the surface of the gelatin solution by 20mm. After the gelatin solution filled the pores of the fibrous membrane, freeze-drying was performed. And (3) setting the temperature of the cold trap to be reduced to-80 ℃, starting a vacuum pump after the temperature of the cold trap is reduced to the set temperature, performing freeze drying, removing the solvent and obtaining a freeze-dried product, wherein the freeze-drying time is 60 hours (2.5 days). And (3) crosslinking gelatin in the dried product by using carbodiimide/N-hydroxysuccinimide, wherein the crosslinking condition is modification treatment for 60 hours at 30 ℃, and after the crosslinking agent is removed by washing with deionized water, freeze drying is carried out again to finally obtain the absorbable sponge dressing with the double-layer structure. The porosity of the final sponge dressing was 98%. Wherein, the thickness of the sponge dressing is 30mm, the thickness of the composite layer 2 is 10mm, and the moisture absorption amount is about 45 times of the self weight of the sponge dressing.

The effect of the dressing is represented by an animal experiment, the sponge is used for repairing the scald defect of the skin of a mouse, and the result shows that the sponge dressing can well promote tissue repair when fibers and tissues grow together.

Example 4

A gelatin solution with a concentration of 30wt.% was prepared and placed in a temperature-controlled vessel, the temperature being maintained at 45 ℃.

Polylactic acid is selected as a hydrophobic material, chitosan is selected as a hydrophilic material, and the mass ratio of the polylactic acid to the chitosan is 5. Chloroform was selected as the organic solvent to prepare a viscous solution with a final concentration of 20 wt.%. The solution was filled into a syringe and mounted on a propeller pump associated with the electrospinning machine. A gelatin solution with a temperature controlled at 40 ℃ was used as a receiving device, and the depth of the solution was 5mm. The electrostatic spinning was carried out under the conditions of a voltage of 25kV, a forwarding speed of 5mL/h, a reception distance of 30cm, an ambient temperature of 20 ℃ and an ambient humidity of 80%. After the solution having a depth of 5mm was filled with the fiber yarn, the temperature of the gelatin solution vessel was adjusted to 5 ℃ to gel the gelatin. Spinning is continued, and the spun silk forms a film sheet on the surface of the gel, wherein the thickness of the film sheet ranges from 400 to 480 micrometers, and the diameter of the fiber ranges from 0.5 to 20 micrometers.

After spinning is finished, the gelatin-polylactic acid-chitosan compound is subjected to freeze drying integrally, the temperature of a cold trap is set to be reduced to-80 ℃, after the temperature of the cold trap is reduced to the set temperature, a vacuum pump is started, freeze drying is carried out, a solvent is removed, and a freeze-dried product is obtained, wherein the freeze-drying time is 50 hours (about 2.08 days). And crosslinking the gelatin in the dried product by using genipin. Wherein the crosslinking condition is modification treatment for 72h at 40 ℃. After crosslinking, putting the crosslinked product into ethanol for soaking for 100min, then putting the soaked crosslinked product into water for soaking for 100min, and alternately soaking in this way until the whole compound swells to form a block material with the thickness increased by 50 times.

Placing the above swelled block material in a suitable tray, and freezing in an ultra-low temperature refrigerator of-80 deg.C for 48h. Freeze drying the frozen block material to removeThe soaked solvent and the swollen structure of the fiber membrane are reserved, and finally the absorbable sponge dressing with a double-layer structure is obtained. The bulk of the fiber sponge is 2200cm ³ The porosity of the whole sponge dressing was 87%. Wherein, the thickness of sponge dressing is 25mm, and the thickness of composite bed is 5mm, and the moisture absorption capacity is about 30 times of sponge dressing self weight.

The effect of the dressing is represented by adopting an animal experiment, the sponge is used for repairing the skin defect of the diabetic pig, and the result shows that the sponge dressing can well promote tissue repair when the fiber and the tissue grow together.

Example 5

The preparation method comprises the steps of selecting hydrophobic polylactic acid and hydrophilic gelatin in a mass ratio of 5. The solution was filled into a syringe and mounted on a propeller pump associated with the electrospinning machine. The electrostatic spinning was carried out under the conditions of a voltage of 20kV, a forwarding speed of 2.5mL/h, a reception distance of 10cm, an ambient temperature of 25 ℃ and an ambient humidity of 75%. The final film thickness is in the range of 300-450 microns and the fiber diameter is in the range of 2.5-50 microns.

And putting the fiber membrane into propylene glycol for soaking for 100min, then putting the soaked fiber membrane into water for soaking for 100min, and alternately soaking until the fiber membrane swells to form a block material with the thickness increased by 70 times. The swollen bulk material was placed in a suitable tray and then frozen in a freezer at-80 ℃ for 12h. And freeze-drying the frozen massive material, removing the soaked solvent and reserving the swollen structure of the fiber membrane to form the fiber sponge. The fiber sponge has a bulk of 2000cm ³ /g。

Preparing a gelatin solution with the concentration of 30wt.%, and soaking a part of the fiber sponge in the gelatin solution, wherein the surface of the fiber sponge exceeds the surface of the gelatin solution by 10mm. After the gelatin solution filled the pores of the fibrous membrane, freeze-drying was performed. And (3) setting the temperature of the cold trap to be reduced to-80 ℃, starting a vacuum pump after the temperature of the cold trap is reduced to the set temperature, performing freeze drying, removing the solvent and obtaining a freeze-dried product, wherein the freeze-drying time is 48 hours (2 days). And (3) carrying out cross-linking treatment on gelatin in the dried product by using formaldehyde, wherein the cross-linking condition is modification treatment for 12 hours at 30 ℃, washing by using deionized water to remove a cross-linking agent, and then carrying out freeze drying again to finally obtain the absorbable sponge dressing with the double-layer structure. The porosity of the final sponge dressing was 95%. Wherein, the thickness of sponge dressing is 15mm, and the thickness of composite bed 2 is 5mm, and the moisture absorption capacity is about 35 times of sponge dressing self weight.

The effect of the dressing is represented by an animal experiment, the sponge is used for repairing the wound surface defect of the diabetic pig, and the result shows that the sponge dressing can well promote tissue repair when fibers and tissues grow together.

Example 6

A gelatin solution with a concentration of 40wt.% was prepared and placed in a temperature-controlled vessel, the temperature being maintained at 45 ℃.

Polyglycolide is used as a hydrophobic material, gelatin is used as a hydrophilic material, and the mass ratio of the polyglycolide to the gelatin is 1. Hexafluoroisopropanol was selected as the organic solvent to prepare a viscous solution with a final concentration of 5 wt.%. The solution was filled into a syringe and mounted on a propeller pump associated with the electrospinning machine. A gelatin solution with a temperature controlled at 40 ℃ is used as a receiving device, and the depth of the solution is 5mm. The electrostatic spinning was carried out under the conditions of a voltage of 40kV, a forwarding speed of 8mL/h, a reception distance of 40cm, an ambient temperature of 20 ℃ and an ambient humidity of 60%. After the solution of 3mm depth was filled with the filaments, the temperature of the gelatin solution vessel was adjusted to 5 ℃ to gel the gelatin. Spinning is continued, and the spun silk forms a film sheet on the surface of the gel, wherein the thickness of the film sheet ranges from 100 to 250 micrometers, and the diameter of the fiber ranges from 0.5 to 10 micrometers.

After spinning is finished, the gelatin-polyglycolide-gelatin compound is subjected to freeze drying integrally, the temperature of a cold trap is set to be reduced to-60 ℃, after the temperature of the cold trap is reduced to the set temperature, a vacuum pump is started for freeze drying, a solvent is removed, and a freeze-dried product is obtained, wherein the freeze-drying time is 48 hours (2 days). And (3) crosslinking the gelatin in the dried product by using glutaraldehyde. Wherein the crosslinking condition is modification treatment for 24h at 20 ℃. After crosslinking, putting the crosslinked product into methanol for soaking for 60min, then putting the soaked crosslinked product into water for soaking for 60min, and alternately soaking in this way until the whole compound swells to form a block material with the thickness increased by 30 times.

Placing the swelled block material in a suitable tray, and freezing in an ultra-low temperature refrigerator at-80 deg.C for 48h. And (3) freeze-drying the frozen massive material, removing the soaked solvent and reserving the structure of the fiber membrane after swelling, and finally obtaining the absorbable sponge dressing with the double-layer structure. The bulk of the fiber sponge is 1000cm ³ The porosity of the whole sponge dressing is 85 percent. Wherein, the thickness of sponge dressing is 10mm, and the thickness of composite bed 2 is 3mm, and the moisture absorption capacity is about 25 times of sponge dressing self weight.

It should be noted that, although the technical solutions of the present invention are described by specific examples, those skilled in the art can understand that the present invention should not be limited thereto.

While embodiments of the present invention have been described above, the above description is illustrative, not exhaustive, and not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen in order to best explain the principles of the embodiments, the practical application, or improvements made to the technology in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. A sponge dressing, comprising:

a matrix comprising interwoven filaments; and

a composite layer formed on at least one surface of the substrate, the composite layer being obtained by filling a part of the substrate with a crosslinked degradable natural polymer material; and is

In the direction perpendicular to the sponge dressing, the maximum length of the composite layer is set to be H ₂ Assuming that the maximum length of the sponge dressing is H ₁ Then H is ₂ And H ₁ The ratio of (1);

the sponge dressing has one or more of the following characteristics:

the moisture absorption amount of the sponge dressing is 10-50 times of the self weight of the sponge dressing, and the porosity of the sponge dressing is 80-99%;

the bulk of the substrate is 300-3000 cm ³ /g。

2. The sponge dressing of claim 1, wherein the filaments are compounded with a hydrophilic material and a hydrophobic material.

3. The sponge dressing of claim 2, wherein the mass ratio of the hydrophobic material to the hydrophilic material is 9.

4. The sponge dressing of claim 2, wherein the hydrophilic material comprises one or a combination of two or more of polyvinyl alcohol, collagen, gelatin, chitosan, starch, agar; and/or

5. The sponge dressing of any of claims 1-3, wherein the cross-linking is in the presence of a cross-linking agent.

6. A method of manufacturing a sponge dressing according to any of claims 1 to 5, comprising the step of forming a composite layer on at least one surface of the substrate.

7. The method of manufacturing according to claim 6, comprising the steps of:

a step of obtaining a substrate;

8. The method according to claim 7, wherein the substrate is prepared by the following method:

alternately infiltrating the fiber material in a first solvent and a second solvent to swell the fiber filaments to obtain a swelling product, wherein the first solvent and the second solvent are different;

freezing the swollen product to obtain a frozen product;

9. The method of manufacturing according to claim 6, comprising the steps of:

after spinning is finished, carrying out freeze drying treatment, and carrying out crosslinking treatment on the degradable natural high polymer material to obtain a crosslinking treatment product;

alternately infiltrating the crosslinked product in a first solvent and a second solvent to swell the fiber yarns to obtain a swelled product, wherein the first solvent and the second solvent are different;

freezing the swollen product to obtain a frozen product;

10. The method according to any one of claims 7 to 9, wherein the concentration of the degradable natural polymer material in the solution containing the degradable natural polymer material is 10 to 50wt%.